TOXIC EFFECTS OF BENZOPYRENE ON IMMUNOCOMPETENT CELLS

苯并芘对免疫活性细胞的毒性作用

基本信息

批准号：
3252455
负责人：
LAWRENCE B SCHOOK
金额：
$ 9.6万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 1988-04-30
项目状态：
已结题

项目摘要

The proposed research deals with the basic mechanisms of the toxic effects of Benzopyrenes on the immune system. It has been previously demonstrated that the polycyclic aromatic hydrocarbons (PAHs) exert suppressive effects upon immunocompetence as well as being potent carcinogens. Previous studies have relied on mixed populations of cells to define the toxicologic actions of PAHs, and Benzopyrenes in particular, on immuno competent cells. It is the goal of this research to delineate the suppressive effect of benzo(a)pyrene using purified populations of cells and defined functional assays and to identify the ultimate macromolecular targets of benzopyrene-induced effects. Once the target cell(s) are identified, the mechanism(s) of alteration will be investigated. Studies are designed to determine if T or B lymphocyte populations and subpopulations are compromised in number, expression of cell surface antigens, ability to produce and respond to soluble mediators, to repond to antigens and to regulate cellular interactions. Studies are also designed to identify differences in Benzopyrene-DNA adduct formation in affected target cell populations versus unaffected populations. Macromolecular synthesis and expression of cell surface proteins will be examined in identified target cell populations from Benzo(a)pyrene-exposed and normal animals. The immunomodulatory effects of the carcinogenic benzopyrenes will be compared to the effects of selected noncarcinogenic congeners. These studies should allow us to rigorously define the target cells and basic mechanisms of benzopyrene immunomodulation. In addition, the effects of the carcinogenic and noncarcinogenic benzopyrenes can be related to differences in their mode of action on immunocompetent cells. This information should contribute to our knowledge of cellular regulation in the immune system. Furthermore, these studies will begin to relate structure of the benzopyrenes to their immunomodulating activity in defined populations of cells.

拟议的研究涉及毒性作用的基本机制苯并芘对免疫系统的影响。之前已经证明过多环芳烃 (PAH) 具有抑制作用具有免疫功能并且是强致癌物。以前的研究依赖于混合细胞群来定义毒理学 PAH，特别是苯并芘，对免疫能力的作用细胞。本研究的目的是描述抑制作用使用纯化的细胞群测定苯并(a)芘并定义功能测定并确定最终的大分子靶标苯并芘引起的影响。一旦目标细胞被识别，将调查改变的机制。研究旨在确定 T 或 B 淋巴细胞群和亚群是否细胞表面抗原的数量、表达、能力受到损害产生并响应可溶性介质，响应抗原和调节细胞相互作用。研究还旨在确定受影响的靶细胞中苯并芘-DNA 加合物形成的差异人群与未受影响的人群。高分子合成与将在确定的靶标中检查细胞表面蛋白的表达来自苯并(a)芘暴露和正常动物的细胞群。这将比较致癌苯并芘的免疫调节作用选定的非致癌同系物的影响。这些研究应该使我们能够严格定义靶细胞并苯并芘免疫调节的基本机制。另外，效果苯并芘的致癌性和非致癌性可能与它们对免疫活性细胞的作用方式存在差异。这这些信息应该有助于我们了解细胞调控免疫系统。此外，这些研究将开始涉及苯并芘的结构及其免疫调节活性的定义细胞群。